Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15

Background

Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15.

Methods and Findings

Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0–2 years and BMI from 2–10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL- and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0–2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5–10), and were largely mediated by fat mass at age 15.

Conclusion

Changes in PI/BMI from 0–10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5–10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight.     

Identification of a ligand for the c-kit proto-oncogene.

We report the purification and N-terminal amino acid sequence of a novel mast cell growth factor, termed MGF, from the supernatants of a murine stromal cell line. A panel of interleukin 3-dependent cell lines were screened for responsiveness to partially purified MGF in [3H]thymidine incorporation assays; proliferative stimulation of these cells in response to MGF correlated with expression of mRNA for the c-kit protooncogene. MGF was shown to be a ligand for c-kit by cross-linking 125I-labeled MGF to c-kit-expressing cells with subsequent immunoprecipitation of the complex with antiserum specific for the C-terminus of c-kit. This establishes MGF as a ligand for the c-kit protein.     

Detection of Candida antigen in bronchoalveolar lavage fluid

While bronchoalveolar lavage is frequently performed to evaluate immunocompromised hosts for infection, the significance of rare yeasts found on the cytologic examination of lavage fluid is unclear. This study used the latex agglutination method to test lavage fluids for Candida antigen to assess its usefulness in distinguishing Candida pneumonia from Candida colonization of the respiratory tract or oral contamination of the lavage specimen. Ninety-seven specimens from 87 patients were categorized on the basis of historical, microbiologic, cytologic and serologic data. Bronchoalveolar lavage fluids were positive for Candida antigen in 0 of 20 specimens from normal controls, 0 of 14 specimens from patient controls, 5 (36%) of 14 specimens from patients with Pneumocystis carinii pneumonia, 0 of 5 specimens from patients with gastrointestinal candidiasis, 0 of 9 specimens contaminated by oral-derived yeasts, 2 (10%) of 19 specimens from patients with probable Candida colonization and 15 (94%) of 16 specimens from patients with clinical and laboratory evidence of Candida pneumonia. We conclude that this test assists in the differentiation of Candida pneumonia from other situations in which yeasts are recovered by bronchoalveolar lavage.     

Central mechanisms of visceral pain

Deep pain arising from muscle, joints, connective tissue, and the viscera is different in character and quality from pain arising from cutaneous structures. Deep pains, particularly visceral pain, are poorly localized, typically referred or transferred to a cutaneous site, and generally produce strong emotional and autonomic responses and tonic muscle contractions. Despite the prevalence and clinical importance of deep pains, it is only relatively recently that investigative efforts have begun to focus on the mechanisms of deep pain. The present report briefly reviews the development and use of a model of visceral pain that employs constant pressure distension of the colon and rectum as a noxious stimulus. Converging behavioral, pharmacological, and physiological evidence that colorectal distension is a valid, reliable, noxious, visceral stimulus is presented.     

Rtm1: A Member of a New Family of Telomeric Repeated Genes in Yeast

We have isolated a new yeast gene called RTM1 whose overexpression confers resistance to the toxicity of molasses. The RTM1 gene encodes a hydrophobic 34-kD protein that contains seven potential transmembrane-spanning segments. Analysis of a series of industrial strains shows that the sequence is present in multiple copies and in variable locations in the genome. RTM loci are always physically associated with SUC telomeric loci. The SUC-RTM sequences are located between X and Y' subtelomeric sequences at chromosome ends. Surprisingly RTM sequences are not detected in the laboratory strain X2180. The lack of this sequence is associated with the absence of any SUC telomeric gene previously described. This observation raises the question of the origin of this nonessential gene. The particular subtelomeric position might explain the SUC-RTM sequence amplification observed in the genome of yeasts used in industrial biomass or ethanol production with molasses as substrate. This SUC-RTM sequence dispersion seems to be a good example of genomic rearrangement playing a role in evolution and environmental adaptation in these industrial yeasts.     

Fitness effects of new mutations in Chlamydomonas reinhardtii across two stress gradients

Most spontaneous mutations affecting fitness are likely to be deleterious, but the strength of selection acting on them might be impacted by environmental stress. Such stress‐dependent selection could expose hidden genetic variation, which in turn might increase the adaptive potential of stressed populations. On the other hand, this variation might represent a genetic load and thus lead to population extinction under stress. Previous studies to determine the link between stress and mutational effects on fitness, however, have produced inconsistent results. Here, we determined the net change in fitness in 29 genotypes of the green algae Chlamydomonas reinhardtii that accumulated mutations in the near absence of selection for approximately 1000 generations across two stress gradients, increasing NaCl and decreasing phosphate. We found mutational effects to be magnified under extremely stressful conditions, but such effects were specific both to the type of stress and to the genetic background. The detection of stress‐dependent fitness effects of mutations depended on accurately scaling relative fitness measures by generation times, thus offering an explanation for the inconsistencies among previous studies.